Anahid Safari1,2, Mehdi Fazeli2, Mohammad Reza Namavar3,4,5, Nader Tanideh6,7, Peyman Jafari8, Afshin Borhani-Haghighi3,9. 1. Endocrinology and Metabolism Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. 2. Department of Pharmacology, Shiraz University, Shiraz, Iran. 3. Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. 4. Histomorphometry and stereology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. 5. Departmentof Anatomy, Shiraz University of Medical Sciences, Shiraz, Iran. 6. Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. 7. Department of Pharmacology, Shiraz University of Medical Sciences, Shiraz, Iran. 8. Department of Biostatistics, Shiraz University of Medical Sciences, Shiraz, Iran. 9. Department of Neurology, Shiraz University of Medical Sciences, Shiraz, Iran.
Abstract
BACKGROUND: Dimethyl fumarate (DMF) has immune-modulatory and neuro-protective characteristics that can be used for treatment of acute ischemic stroke. OBJECTIVE: To investigate the therapeutic effects of DMF on histological and functional recovery of rats after transient middle cerebral artery (MCA) occlusion. METHODS: 22 Sprague-Dawley male rats weighing 275-300 g were randomized into three groups by block randomization. In the sham group (n = 7), the neck was opened, but neither MCA was occluded, nor any drug was administered.The control group (n = 7) was treated with vehicle (methocel) by gavage for 14 days after MCA occlusion. In the DMF-treated group (n = 8), treatment was performed with 15 mg/kg body weight dimethyl fumarate twice a day for 14 days after MCA occlusion. Transient occlusion of the right MCA was performed by intraluminal thread method in the DMF-treated and the control group. Neurological deficit score (NDS), pole test, and adhesive removal test were performed before the surgery, and on post-operative Days 0, 3, 5, 7, 10, and 14. After the final behaviour test, the animals' brains were perfused and removed. Brains were frozen and sectioned serially and coronally using a cryostat. Infract volume and brain volume were estimated by stereology. RESULTS: The percentage of infarct volume was significantly lower in DMF-treated animals (5.76%) than in the control group (22.39%) (P < 0.0001). Regarding behavioural tests, the DMF-treated group showed better function in NDS on Days 7 (P = 0.041) and 10 (P = 0.046), but not in pole and adhesive removal tests. There was no significant correlation between behavioural tests and histological results. CONCLUSION: Dimethyl fumarate could be beneficial as a potential neuroprotective agent in the treatment of stroke.
BACKGROUND:Dimethyl fumarate (DMF) has immune-modulatory and neuro-protective characteristics that can be used for treatment of acute ischemic stroke. OBJECTIVE: To investigate the therapeutic effects of DMF on histological and functional recovery of rats after transient middle cerebral artery (MCA) occlusion. METHODS: 22 Sprague-Dawley male rats weighing 275-300 g were randomized into three groups by block randomization. In the sham group (n = 7), the neck was opened, but neither MCA was occluded, nor any drug was administered.The control group (n = 7) was treated with vehicle (methocel) by gavage for 14 days after MCA occlusion. In the DMF-treated group (n = 8), treatment was performed with 15 mg/kg body weight dimethyl fumarate twice a day for 14 days after MCA occlusion. Transient occlusion of the right MCA was performed by intraluminal thread method in the DMF-treated and the control group. Neurological deficit score (NDS), pole test, and adhesive removal test were performed before the surgery, and on post-operative Days 0, 3, 5, 7, 10, and 14. After the final behaviour test, the animals' brains were perfused and removed. Brains were frozen and sectioned serially and coronally using a cryostat. Infract volume and brain volume were estimated by stereology. RESULTS: The percentage of infarct volume was significantly lower in DMF-treated animals (5.76%) than in the control group (22.39%) (P < 0.0001). Regarding behavioural tests, the DMF-treated group showed better function in NDS on Days 7 (P = 0.041) and 10 (P = 0.046), but not in pole and adhesive removal tests. There was no significant correlation between behavioural tests and histological results. CONCLUSION:Dimethyl fumarate could be beneficial as a potential neuroprotective agent in the treatment of stroke.
Authors: Mirjam Dreikorn; Zeljko Milacic; Vladimir Pavlovic; Sven G Meuth; Christoph Kleinschnitz; Peter Kraft Journal: Ther Adv Neurol Disord Date: 2018-04-20 Impact factor: 6.570